In vitro dissolution, Alternative Methods.pptx

Dissolution is a important tool, that can be used for determining the drug release rate of drug.

1. IN VITRO DISSOLUTION AND DRUG RELEASE TESTING Submitted By: Prachi Pandey Submitted To: Dr. Tejpal Yadav M. Pharm (Pharmaceutics), IInd Sem. In-vitro dissolution testing is a very powerful tool to easily and effectively obtain information about the performance of drug products.

2. DEFINATION Dissolution is a process in which a solid substance solubilizes in a given solvent (mass transfer from the solid surface to the liquid phase.) Dissolution testing measures the extent and rate of solution formation from a dosage form, such as tablet, capsule, ointment, etc. The dissolution of a drug is important for its bioavailability and therapeutic effectiveness

3. NON SINK METHODS For poorly water-soluble drugs, pharmaceutical scientists are increasingly applying in vitro dissolution testing under non-sink conditions for a direct evaluation of their ability to generate and maintain supersaturation as a predictive surrogate for ensuring product quality and in vivo performance. NATURAL CONVECTION NON SINK METHODS: a) Klein solvmeter method b) Nelson hanging pellet method c) Levy static disk method ALTERNATIVE METHOD OF DISSOLUTION

4. FORCED CONVECTION NON SINK METHODS: Tumbling method Levy or Beaker method Rotating disk method Particle size method USP Rotating basket apparatus USP Paddle apparatu NON-SINK METHODS

5. SINK METHOD Sink condition is the ability of the dissolution media to dissolve at least 3 times the amount of drug that is in your dosage form. Having sink conditions helps your dissolution have more robustness as well as being more biologically relevant. FORCED CONVECTION SINK DEVICES: Wurster pollis adsorption method Partition method Dialysis methods Rotating disk apparatus Sink method

6. SINK METHOD CONTINOUS FLOW/FLOW THROUGH METHODS: Pernarowski method Langenbucher method Baun and Walker Tingstad and Reigelman Modified column apparatus Takenaka method

7. Non-SINK METHOD - KLEIN SOLVMETER METHOD KLEIN SOLVMETER METHOD Carrier device surrounded by flat and is immersed in dissolution medium When dosage form is placed in the boat the bar moves and as dosage form dissolves it moves upwards Amount of dosage form dissolved is revealed from the difference in height of bar movemen Figure (a) Klein solvmeter Method

8. NELSON HANGING PELLET METHOD Aluminum strip having provision for holding dosage form which is in turn connected perfectly maintained balance arm of strip Dosage form is mounted on aluminium strip with help of wax .This method can be employed to know Intrinsic dissolution rate. To prevent disintegration further high pressures can be applied and also constant surface NELSON HANGING PELLET METHOD Figure ( b ) Nelson Hanging Pellet Method

9. Levy Static disk method LEVY STATIC DISK METHOD Acrylic holder containing dosage form is inserted into a known volume of medium through rubber stopper The vial is inverted and placed in incubator at 37 C. At specific time intervals the vial is removed from incubator and samples are analysed Disadvantages:- effect of conc. On dissolution medium is ignored and the surface area of dosage form while dissolving is assumed constant which is not impractical. Figure ( c ) Levy Static Disk Method

10. Sink METHOD- WURSTER- POLLI ADSORPTION METHOD WURSTER- POLLI ADSORPTION METHOD In this method the dissolved drug is adsorbed by charcoal or bentonite, care should be taken regarding the adsorbent, adsorbent should not alter the viscorsity of the medium. Figure ( d ) Wurster- Polli adsorption method

11. PARTITION METHOD In this device organic phase is employed to remove the dissolved drug such that the drug would partition between the lipophilic and hydrophilic phases. selection of organic phase plays a critical role PARTITION METHOD Figure (c) Partition Method

12. ROTATING FLASK APPARATUS In this method a flask containing dissolution medium is rotated around its horizontal axis in a water bath kept at a temperature of 37 C. The flask has a provision of sampling such that aliquots can be withdrawn and the fresh medium can be replaced back. This apparatus is best suited for oral solid dosage forms like tablets and capsules since they do not require much agitation. ROTATING FLASK APPARATUS Figure (c) Receprocating cylinder type

13. FLOW THROUGH DEVICES FLOW THROUGH DEVICES For the drugs which saturate rapidly in large volumes of medium, USP apparatus will not serve the purpose. For this the suitable device is flow through device. In this device unlimited quantity of fresh dissolution is available. A dosage form is placed in a small cell and is subjected to a stream of fresh dissolution media. Figure (d) Flow through cell Method

14. PERNAROWSKI PERNAROWSKI It consists of 10 mesh stainless steel basket stirrer assembly with an adjustable stirrer. T he chamber is 3 necked flask of 33 mm and the rest two of 20 mm diameter. 1 L of medium is employed within the flask. T he dissolution characteristics are dependent upon the amount of medium pumped through the dissolution chamber.

15. LANGENBUCHER COLUMN TYPE LANGENBUCHER COLUMN TYPE This device is according to the dissolution basic design. The screen is constructed such that the medium flows equally through the entire cross section in a laminar pattern. This is again closed by a secondary screen, filter which prevents the undissolved drug from being eluted.

16. TINGSTAD AND RIEGELMAN TINGSTAD AND RIEGELMAN A cylindrical glass cell of 6.1 cm long and 1.9 cm in diameter constructed with two glass filter funnels is used. The dissolution cell has filter membranes which prevents the solid particles from being analyzed. There are also external valves to control the excess flow of solvent into the system. the air trap averts air bubbles. The complete assembly is immersed in a temperature bath kept at 37°C Figure ( e ) Tingstad and riegelman

17. MODIFIED COLUMN APPARATUS Figure (f) Modified Column Apparatus MODIFIED COLUMN APPARATUS The device consists of filter of 14 M -size made of nylon. T he tubing from the pump is connected to the dissolution cell. T he Teflon faced stainless steel supports the screen resting on the bottom half of the filter holder. The direction of the flow is such that the particles do not fall through the screen. the rest of the process is the same.

18. TAKENAKA TAKENAKA The release of drug is measured with the aid of in vitro simulator device consisting of flow type dissolution container. The dosage form is placed in the basket rotating at 94 rpm with 300 ml of medium. then the medium is removed by collecting reservior using peristaltic pump. aliquots are withdrawn using syringe and then filtered using Whatman filter paper and the same volume is replaced immediately with fresh medium. Figure (g) Takenaka

19. IN VITRO DISSOLUTION AND DRUG RELEASE STUDY INVOLVES IN VITRO DISSOLUTION AND DRUG RELEASE STUDY INVOLVES Preparation of solutions for calibration curve Stock solution Sample solution Buffer solution Determination of absorption maxima Preparation of calibration curve Dissolution study Dissolution procedure was carried out. Plot a graph between Time intervals on x-axis vs % of drug release on y-axis. Find out the slope, concentration, amount of drug release, percentage of drug release and report it.

20. Graphic Representation of in vitro dissolution testing

21. DRUG RELEASE TESTING Drug release is the process by which a drug leaves a drug product Drug release: Immediate release (IR) Sustained Release (SR) Sustained Action (SA) Extended Release (ER) Long Acting (LA) Prolong Action (PA) Controlled Release (CR) Timed Release (TR)

22. Immediate release drug products allow drugs to dissolve with no intention of delaying or prolonging dissolution or absorption of the drug Prolonged-release dosage forms Prolonged-release dosage forms are modified-release dosage forms showing a slower release of the active substance(s) than that of a conventional-release dosage form administered by the same route. • Delayed release is defined as the release of a drug at a time other than immediately following administration. • Enteric Coated: Intended to delay the release of the drug (or drugs) until the dosage form has passed through the stomach. Enteric-coated products are delayed-release dosage forms. DRUG RELEASE

23. Controlled release includes extended-release and pulsatile-release products Extended-release products are formulated to make the drug available over an extended period after administration. Pulsatile release involves the release of finite amounts (or pulses) of drug at distinct time intervals that are programmed into the drug product. Repeat action products contain two single doses of medication; one for immediate release; another one for modified release DRUG RELEASE

24. T argeted release drug release directed toward isolating or concentrating a drug in a body region, tissue or site of absorption or for drug action Drug release and dissolution Modified-release dosage forms include both delayed and extended-release drug productsModified-release dosage forms are preparations where the rate and/or place of release of the active substance(s) is different from that of a conventional- release dosage form administered by the same route. DRUG RELEASE

25. IN VITRO DRUG RELEASE TESTING ROTATING BASKET METHOD: In vitro release study was carried out by the rotating basket method. Six tablets of each batch were taken and placed in rotating basket, respectively. Then the rotating basket was introduced into 900 mL of each dissolution medium (water, 0.1 M HCI and pH 6.8 phosphate buffer) at 37°C ± 0.5°C with a rotation speed of 100 rpm. 5 mL of sample solution was collected a different time intervals (2, 4, 6, 8, 10, 12 h) and filtered through a 0.45 um hydrophilic membrane. IN VITRO DRUG RELEASE TESTING

26. 1.0 mL of subsequent filtrate was taken accurately to add into a 100 mL volumetric flask and diluted with the corresponding dissolution medium to 100 mL and mixed well. The amount of drug dissolved in the dissolution medium was measured using an UV-visible spectrophotometer at 233 nm. The same volume of fresh dissolution medium at the same temperature was added to replace the amount withdrawn after each sampling. The drug amount of cumulative release was calculated with a standard curve. IN VITRO DRUG RELEASE TESTING